In vitro preliminary study on different anti-PD-1 antibody concentrations on T cells activation.

Lung adenocarcinoma predominates among diagnosed nonsmall cell lung cancer subtypes in nonsmokers. The introduction of immune checkpoint inhibitors into clinical practice offered patients prolonged progression-free survival and overall survival times. However, the results demonstrate that the benefits do not apply to all patients. Nivolumab is a monoclonal antibody against the PD-1 protein expressed mainly on T lymphocytes and is widely used in cancer therapy in different settings. Tumor cells often express the PD-L1 molecule and can effectively block the action of PD-1-positive lymphocytes. A body of knowledge regarding the high expression of PD-L1 on tumor cells highlights that it does not always correlate with the effectiveness of anti-PD-1 therapy. The side effects of the therapy also constitute a significant issue. These side effects can occur at any time during anti-PD-1 treatment and lead to discontinuation and even the death of the patient. In these situations, it is possible to delay the dosage. Nevertheless, unfortunately, it is not possible to reduce the dose of anti-PD-1 antibody, which would undoubtedly minimize side effects, leaving the patient's immune system active. In our preliminary study, we analyzed the effect of different concentrations of nivolumab on the functioning of T lymphocytes. Activation and proliferation markers were investigated on T cells after being cultured with antigen-stimulated autologous dendritic cells. This process may indicate an appropriate concentration of nivolumab, which shows clinical activity with minimal side effects.

Clinical Application Perspectives of Lung Cancers 3D Tumor Microenvironment Models for In Vitro Cultures.

Despite the enormous progress and development of modern therapies, lung cancer remains one of the most common causes of death among men and women. The key element in the development of new anti-cancer drugs is proper planning of the preclinical research phase. The most adequate basic research exemplary for cancer study are 3D tumor microenvironment in vitro models, which allow us to avoid the use of animal models and ensure replicable culture condition. However, the question tormenting the scientist is how to choose the best tool for tumor microenvironment research, especially for extremely heterogenous lung cancer cases. In the presented review we are focused to explain the key factors of lung cancer biology, its microenvironment, and clinical gaps related to different therapies. The review summarized the most important strategies for in vitro culture models mimicking the tumor-tumor microenvironmental interaction, as well as all advantages and disadvantages were depicted. This knowledge could facilitate the right decision to designate proper pre-clinical in vitro study, based on available analytical tools and technical capabilities, to obtain more reliable and personalized results for faster introduction them into the future clinical trials.

Immunoprofiling: An Encouraging Method for Predictive Factors Examination in Lung Cancer Patients Treated with Immunotherapy.

The efficiency of immunotherapy using monoclonal antibodies that inhibit immune checkpoints has been proven in many clinical studies and well documented by numerous registration approaches. To date, PD-L1 expression on tumor and immune cells, tumor mutation burden (TMB), and microsatellite instability (MSI) are the only validated predictive factors used for the qualification of cancer patients for immunotherapy. However, they are not the ideal predictive factors. No response to immunotherapy could be observed in patients with high PD-L1 expression, TMB, or MSI. On the other hand, the effectiveness of this treatment method also may occur in patients without PD-L1 expression or with low TMB and with microsatellite stability. When considering the best predictive factor, we should remember that the effectiveness of immunotherapy relies on an overly complex process depending on many factors. To specifically stimulate lymphocytes, not only should their activity in the tumor microenvironment be unlocked, but above all, they should recognize tumor antigens. The proper functioning of the anticancer immune system requires the proper interaction of many elements of the specific and non-specific responses. For these reasons, a multi-parameter analysis of the immune system at its different activity levels is considered a very future-oriented predictive marker. Such complex immunological analysis is performed using modern molecular biology techniques. Based on the gene expression studies, we can determine the content of individual immune cells within the tumor, its stroma, and beyond. This includes all cell types from active memory cytotoxic T cells, M1 macrophages, to exhausted T cells, regulatory T cells, and M2 macrophages. In this article, we summarize the possibilities of using an immune system analysis to predict immunotherapy efficacy in cancer patients. Moreover, we present the advantages and disadvantages of immunoprofiling as well as a proposed future direction for this new method of immune system analysis in cancer patients who receive immunotherapy.

Aptamers in Non-Small Cell Lung Cancer Treatment.

Aptamers are short, single-stranded oligonucleotides which are capable of specifically binding to single molecules and cellular structures. Aptamers are also known as "chemical antibodies". Compared to monoclonal antibodies, they are characterized by higher reaction specificity, lower molecular weight, lower production costs, and lower variability in the production stage. Aptamer research has been extended during the past twenty years, but only Macugen® has been accepted by the Food and Drug Administration (FDA) to date, and few aptamers have been examined in clinical trials. In vitro studies with aptamers have shown that they may take part in the regulation of cancer progression, angiogenesis, and metastasis processes. In this article, we focus on the potential use of aptamers in non-small cell lung cancer treatment.